Distinct patterns of glia repair and remyelination in antibody-mediated demyelination models of multiple sclerosis and neuromyelitis optica

Glia
Yiting LiuJeffrey L Bennett

Abstract

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory demyelinating disorders of the central nervous system with evidence of antibody-mediated pathology. Using ex vivo organotypic mouse cerebellar slice cultures, we have demonstrated that recombinant antibodies (rAbs) cloned from cerebrospinal fluid plasmablasts of MS and NMO patients target myelin- and astrocyte-specific antigens to induce disease-specific oligodendrocyte loss and myelin degradation. In this study, we examined glial cell responses and myelin integrity during recovery from disease-specific antibody-mediated injury. Following exposure to MS rAb and human complement (HC) in cerebellar explants, myelinating oligodendrocytes repopulated the demyelinated tissue and formed new myelin sheaths along axons. Remyelination was accompanied by pronounced microglial activation. In contrast, following treatment with NMO rAb and HC, there was rapid regeneration of astrocytes and pre-myelinating oligodendrocytes but little formation of myelin sheaths on preserved axons. Deficient remyelination was associated with progressive axonal loss and the return of microglia to a resting state. Our results indicate that antibody-mediated demyelination in MS and NMO show ...Continue Reading

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Citations

Sep 26, 2020·Frontiers in Molecular Neuroscience·Emily J Koller, Paramita Chakrabarty
Nov 24, 2020·Frontiers in Neurology·Yael Redler, Michael Levy
Nov 17, 2020·Frontiers in Neurology·Xiaoli YuYiting Liu
Jun 3, 2021·International Journal of Molecular Sciences·Ulises Gómez-PinedoJorge Matías-Guiu
Jun 20, 2021·Brain : a Journal of Neurology·Kathryn PellerinMichael Mingueneau
Sep 6, 2021·Journal of Neurology·Hesham AbboudUNKNOWN On-behalf of the Guthy-Jackson Foundation NMO International Clinical Consortium

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